Identification of a set of genes associated with response to interleukin-2 and interferon-α combination therapy for renal cell carcinoma through genome-wide gene expression profiling

Mizumori,Osamu; Zembutsu,Hitoshi; Kato,Yoichiro; Tsunoda,Tatsuhiko; Miya,Fuyuki; Morizono,Takashi; Tsukamoto,Taiji; Fujioka,Tomoaki; Tomita,Yoshihiko; Kitamura,Tadaichi; Ozono,Seiichiro; Miki,Tsuneharu; Naito,Seiji; Akaza,Hideyuki; Nakamura,Yusuke

doi:10.3892/etm.2010.148

November-December 2010 Volume 1 Issue 6

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

November-December 2010 Volume 1 Issue 6

Full Size Image

Article

Identification of a set of genes associated with response to interleukin-2 and interferon-α combination therapy for renal cell carcinoma through genome-wide gene expression profiling

Authors:
- Osamu Mizumori
- Hitoshi Zembutsu
- Yoichiro Kato
- Tatsuhiko Tsunoda
- Fuyuki Miya
- Takashi Morizono
- Taiji Tsukamoto
- Tomoaki Fujioka
- Yoshihiko Tomita
- Tadaichi Kitamura
- Seiichiro Ozono
- Tsuneharu Miki
- Seiji Naito
- Hideyuki Akaza
- Yusuke Nakamura
View Affiliations / Copyright

Affiliations: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan, Laboratory for Medical Informatics, Center for Genomic Medicine, RIKEN, Kanagawa 230-0045, Japan, Department of Urologic Surgery and Andrology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan, Department of Urology, Iwate Medical University, School of Medicine, Iwate 020-8505, Japan, Department of Urology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan, Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan, Department of Urology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan, Department of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan, Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan, Department of Urology and Andrology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaragi 305-8577, Japan
Pages: 955-961
|
Published online on: September 10, 2010

https://doi.org/10.3892/etm.2010.148
Expand metrics +

Abstract

Interleukin (IL)-2 and interferon (IFN)-α combination therapy for metastatic renal cell carcinoma (RCC) improves the prognosis for a subset of patients, while some patients suffer from severe adverse drug reactions with little benefit. To establish a method to predict responses to this combination therapy (approximately 30% response rate), the gene expression profiles of primary RCCs were analyzed using an oligoDNA microarray consisting of 38,500 genes or ESTs, after enrichment of the cancer cell population by laser microbeam microdissection. The analysis of 10 responders and 18 non-responders identified 24 genes that exhibited significant differential expression between the two groups. In addition, the patients whose tumors did not express HLA-DQA1 or HLA-DQB1 molecules demonstrated poor clinical response. Exclusion of patients with tumors lacking either of these two genes is likely to improve the response rate to IL-2 and IFN-α combination therapy from 30 to 67%, indicating that a simple pretreatment test provides useful information with which to subselect patients with renal cancer in order to improve the efficacy of this treatment and reduce unnecessary medical costs.

View Figures

View References

1.	Ferlay J, Bray F, Pisani P and Parkin DM: GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5, Version 2.0. IARC Press; Lyon: 2004
2.	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
3.	Motzer RJ, Dror Michaelson M, Redman BG, et al: Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 24:16–24. 2006. View Article : Google Scholar
4.	Motzer RJ, Rini BI, Bukowski RM, et al: Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 295:2516–2524. 2006. View Article : Google Scholar : PubMed/NCBI
5.	Motzer RJ, Hutson TE, Tomczak P, et al: Sunitinib versus inter-feron alpha in metastatic renal-cell carcinoma. N Engl J Med. 356:115–124. 2007. View Article : Google Scholar : PubMed/NCBI
6.	Escudier B, Eisen T, Stadler WM, et al: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 356:125–134. 2007. View Article : Google Scholar : PubMed/NCBI
7.	Szcylik C, Demkow T, Staehler M, et al: Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: final results. J Clin Oncol. 25:50252007.
8.	Aso Y, Tazaki H, Umeda T and Marumo K: A phase II study of S-6820 (recombinant interleukin-2) on renal cell carcinoma (in Japanese). Biotherapy. 3:999–1007. 1989.
9.	Aso Y, Homma Y, Tazaki H, et al: A phase II trial of S-6820 (recombinant interleukin-2) on renal cell carcinoma refractory to interferon (in Japanese). Hinyokigeka. 8:75–86. 1995.
10.	Hayashi T, Miyagawa Y, Tsujimura A, Nonomura N, Minami M and Okuyama A: A case of renal cell carcinoma with multiple lung metastases refractory to interferon-α showing complete remission by interleukin-2 monotherapy. Int J Urol. 13:805–808. 2006.PubMed/NCBI
11.	Kobayashi M, Ikeda H, Nukui A, et al: Clinical outcome and prognostic survival factors in patients with advanced renal cell carcinoma treated with very low-dose interleukin-2, interferon-α and tegafur-uracil: a single-institution experience. Int J Clin Oncol. 13:257–262. 2008.
12.	Wirth MP: Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am. 20:283–295. 1993.PubMed/NCBI
13.	Horoszewicz JS and Murphy GP: An assessment of the current use of human interferons in therapy of urological cancers. J Urol. 142:1173–1180. 1989.PubMed/NCBI
14.	Bukowski RM: Natural history and therapy of metastatic renal cell carcinoma: the role of interleukin-2. Cancer. 80:1198–1220. 1997. View Article : Google Scholar : PubMed/NCBI
15.	Motzer RJ and Russo P: Systemic therapy for renal cell carcinoma. J Urol. 163:408–417. 2000. View Article : Google Scholar : PubMed/NCBI
16.	Klapper JA, Downey SG, Smith FO, et al: High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the Surgery Branch at the National Cancer Institute between 1986 and 2006. Cancer. 113:293–301. 2008.
17.	Belldegrun AS, Klatte T, Shuch B, et al: Cancer-specific survival outcomes among patients treated during the cytokine era of kidney cancer (1989–2005): a benchmark for emerging targeted cancer therapies. Cancer. 113:2457–2463. 2008.PubMed/NCBI
18.	Akaza H, Tsukamoto T, Onishi T, Miki T, Kinouchi T and Naito S: A low-dose combination therapy of interleukin-2 and interferon-α is effective for lung metastasis of renal cell carcinoma: a multi-center open study. Int J Clin Oncol. 11:434–440. 2006.
19.	Akaza H, Kawai K, Tsukamoto T, et al: Successful outcomes using combination therapy of interleukin-2 and interferon-α for renal cell carcinoma patients with lung metastasis. Jpn J Clin Oncol. 40:684–689. 2010.
20.	WHO Handbook for Reporting Results of Cancer Treatment: WHO Offset Publication No. 48. World Health Organization; Geneva: 1979
21.	Japanese Urological Association and Japanese Society of Pathology: Response criteria for urological cancer treatment. Jpn J Urol. 83:447–472. 1992.
22.	Golub TR, Slonim DK, Tamayo P, et al: Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science. 286:531–537. 1999. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Identification of a set of genes associated with response to interleukin-2 and interferon-α combination therapy for renal cell carcinoma through genome-wide gene expression profiling

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Related Articles